Improving the safety of CAR-T-cell therapy: The risk and prevention of viral infection for patients with relapsed or refractory B-cell lymphoma undergoing CAR-T-cell therapy.

Chimeric antigen receptor (CAR) T-cell therapy, an innovative immunotherapeutic against relapsed/refractory B-cell lymphoma, faces challenges due to frequent viral infections. Despite this, a comprehensive review addressing risk assessment, surveillance, and treatment management is notably absent. This review elucidates immune response compromises during viral infections in CAR-T recipients, collates susceptibility risk factors, and deliberates on preventive strategies. In the post-pandemic era, marked by the Omicron variant, new and severe threats to CAR-T therapy emerge, necessitating exploration of preventive and treatment measures for COVID-19. Overall, the review provides recommendations for viral infection prophylaxis and management, enhancing CAR-T product safety and recipient survival.

Application of the Hammersmith Infant Neurological Examination in the developmental follow-up of high-risk infants.

AIM: To investigate the independent influences affecting the global score of the Hammersmith Infant Neurological Examination (HINE) in the early life of high-risk infants and to provide evidence for early effective screening and for evaluating interventions. METHOD: We conducted a prospective cohort study of 258 high-risk infants assessed by the HINE and Gesell Developmental Diagnosis Schedule at 3, 6, 9, and 12 months corrected age. A multiple linear regression model was developed to investigate independent influences on HINE global score at 3 months corrected age. The accuracy of the HINE global score was analysed by calculating the discriminant, concurrent, and predictive validities according to ages. RESULTS: There were nine independent influences affecting the HINE global score at 3 months corrected age in high-risk infants. The discriminant, concurrent, and predictive validities of the HINE for gross motor developmental delays at 12 months corrected age were all statistically significant (p < 0.05). INTERPRETATION: Different neonatal clinical settings are related to the HINE global score of high-risk infants early in life. The HINE can be used for longitudinal monitoring of neurological development in the first year of life in a typical Chinese clinical setting and the findings at all four ages tested relate to neuromotor outcomes at 12 months corrected age.

[Research progress on curcumin improving chronic low-grade inflammation and related diseases].

Chronic low-grade inflammation(CLGI), a relatively new concept without a clear definition, refers to a nonspecific, chronic, continuous, and low-grade inflammation state, and it is closely associated with various chronic diseases, including obesity, inflammatory bowel disease, neurodegenerative diseases, and tumors. Improvement of CLGI can slow down disease progression. Anti-inflammatory treatment is an important strategy for prevention and treatment of CLGI. However, there is currently no definitive drug treatment method. Curcumin is a polyphenolic compound extracted from the rhizome of zingiberaceae, with significant anti-inflammatory activity. Research has shown that curcumin can play an anti-inflammatory role by regulating NF-κB, JAK/STAT, PI3K/Akt, MAPK, NLRP3 inflammasome, Nrf2/ARE, and other inflammation-related pathways. This paper summarized the anti-inflammatory mechanisms, pharmacological effect, and clinical application of curcumin in improving CLGI and other diseases, so as to provide a reference for in-depth research and clinical application of curcumin in improving CLGI.

[New drug discovery and prospect of small nucleic acids derived from traditional Chinese medicine and natural medicine].

Small nucleic acid drugs mainly include small interfering RNA(siRNA), antisense oligonucleotide(ASO), microRNA(miRNA), messenger RNA(mRNA), nucleic acid aptamer(aptamer), and so on. Its translation or regulation can be inhibited by binding to the RNA of the target molecule. Due to its strong specificity, persistence, and curability, small nucleic acid drugs have received considerable attention in recent years. Recent studies have shown that some miRNAs from animal and plant sources can stably exist in the blood, tissue, and organs of animals and human beings and exert pharmacological action by regulating the expression of various target proteins. This paper summarized the discovery of small nucleic acids derived from traditional Chinese medicine(TCM) and natural drugs and their cross-border regulatory mechanisms and discussed the technical challenges and regulatory issues brought by this new drug, which can provide new ideas and methods for explaining the complex mechanism of TCM, developing new drugs of small nucleic acids from TCM and natural medicine, and conducting regulatory scientific research.

[Bioinformatics database and production layout visual analysis platform of medicinal plants:a case study of Dao-di medicinal materials in Sichuan province].

In the new stage of trans-omics and trans-subjects for medicinal plants, it is an urgent need to integrate big data, provide interactive applications, and form a unified and multi-level research system and big data platform. Dao-di medicinal material, as an important source of medicinal plants, is a unique quality concept and comprehensive standard of tranditional Chinese medicine(TCM). Several databases have been developed in China and abroad, such as the Encyclopedia of Traditional Chinese Medicine(ETCM) and the Global Pharmacopoeia Genome Database(GPGD). Yet, most databases do not provide multi-dimensional data, including geographic data, phenotype data, compound data, and genetic data. Sichuan, known as the hometown of TCM therapies and the treasure trove of TCM, is the most representative region of medicinal plant diversity in China. According to the latest data of the fourth national survey of TCM resources, there are more than 8 000 TCM and 86 Dao-di medicinal materials in Sichuan province. Based on resource census data and relevant achievements, this study constructed the bioinformatics database of medicinal plants and the visual analysis platform of production layout by taking the Dao-di medicinal materials in Sichuan province as an example, covering geographic data, phenotype data, compound data, and genetic data. It effectively integrates multi-dimensional data of Dao-di medicinal materials and provides different levels of data interaction applications. The platform is the first large-scale multi-dimensional database and visual platform of Dao-di medicinal materials in Sichuan province, which serves as an essential resource for germplasm resources identification, decomposition of biosynthetic pathways, molecular breeding of varieties and provides medicinal plant resource information and data support for development and utilization of medicinal plants in China and abroad.

Lack of surgical resection is associated with increased early mortality in hematological patients complicated with rhino-orbital-cerebral mucormycosis.

Rhino-orbital-cerebral mucormycosis (ROCM), which is an acute fatal infectious disease with a high mortality rate, is increasingly being diagnosed in patients with hematological diseases worldwide. We aimed to investigate the clinical characteristics, treatment, and prognosis of hematological diseases complicated by ROCM. Our sample comprised a total of 60 ROCM patients with hematological diseases. The most common primary disease was acute lymphoblastic leukemia (ALL) (n=27, 45.0%), while 36 patients (60.0%) were diagnosed with a clear type of pathogen, all belonging to the Mucorales, most commonly Rhizopus (41.7%). Of the 32 patients (53.3%) who died, 19 (59.3%) died of mucormycosis, and 84.2% (n=16) of those died within 1 month. Forty-eight cases (80.0%) received antifungal treatment combined with surgical therapy, 12 of whom (25.0%) died of mucormycosis, amounting to a mortality rate that was significantly lower than in patients who received antifungal therapy alone (n=7, 58.3%) (P=0.012). The median neutrophil value of patients who underwent surgery was 0.58 (0.11-2.80) 103/µL, the median platelet value was 58.00 (17.00-93.00) 103/µL, and no surgery-related deaths were reported. Multivariate analysis showed that patient's advanced age (P=0.012, OR=1.035 (1.008-1.064)) and lack of surgical treatment (P=0.030, OR=4.971 (1.173-21.074)) were independent prognostic factors.In this study, hematological diseases associated with ROCM have a high mortality rate. Lack of surgical treatment is an independent prognostic factor for death from mucormycosis. Surgery may therefore be considered in patients with hematological disease even if their neutrophil and platelet values are lower than normal.

Climate factors and host chemical profiles jointly drives the bacterial community assembly in Mussaenda pubescens stems.

Endophytic bacteria residing within host plants can significantly impact on the host's growth, health, and overall relationship with its surrounding environment. However, the process that shape the community assembly of stem bacterial endophytes (SBEs) remains poorly understood. This study explored the community structure, co-occurrence patterns, and ecological processes of the SBEs inhabiting the shrub host, Mussaenda pubescens, across seven locations in southeastern China. We found that the absolute abundances, alpha diversity, and community composition of SBE communities exhibited notable differences among various host populations. Stem chemical characteristics were the most important factors influencing SBE community distribution, followed by geographic distance and climatic factors. The beta diversity decomposition analyses indicated that SBE community dissimilarities between sites were nearly equally driven by similarity, replacement diversity, and richness difference. The co-occurrence network analysis revealed that the keystone taxa were mostly observed in rare species, which may be essential for preserving the ecosystem's functions. Conditionally abundant taxa (CAT) showcased the highest closeness centrality, while exhibiting the lowest degree centrality and betweenness centrality as opposed to rare taxa. In addition, stochastic processes also played an important role in structuring SBE communities, with ecological drift being the dominant factor for both abundant and rare taxa. This study would deepen our understanding of the ecological dynamics and microbial interactions within plant endophytic microbiomes.

Aplasia Cutis Congenita With Cutaneous Meningioma: A Rare Case.

ABSTRACT: Cutaneous meningioma, characterized by ectopic meningothelial cells in the dermis or subcutis, is a rare neoplasm. Generally, the most common location for cutaneous meningioma is the scalp. We report a case of cutaneous meningioma presenting as soft, light red, atrophic, and smooth patches with central blue spots. On histological examination, the tumor consisted largely of epithelioid cells, whorls, nests, and syncytial sheets of meningothelial cells. HMB-45, Melan-A, and S100 were negative; epithelial membrane antigen and somatostatin receptor 2 were positive. Ultimately, histopathologic examination and immunohistochemistry results supported a diagnosis of cutaneous meningioma. In addition, dermal dysplasia was observed above the tumor, manifested by thinning of the dermis and loss of appendages. No abnormalities were found on brain magnetic resonance imaging. Cutaneous meningioma is an extremely rare tumor, and its manifestation as an atrophic patch is even rarer. There have been mainly clinical reports of cutaneous meningioma. This was a rare case of focal aplasia cutis congenita with cutaneous meningioma. For cutaneous meningioma to be diagnosed earlier, there needs to be greater public awareness about the condition.

[Relationship Between Dynamic Compliance and Airway Resistance and Infection Indicators in Elderly Patients With Lung Infection After Radiotherapy for Esophageal Cancer]. / è€å¹´é£Ÿç®¡ç™Œæ‚£è€ æ”¾ç–—åŽè‚ºåŠ¨æ€é¡ºåº”æ€§ã€æ°”é“é˜»åŠ›ä¸Žè‚ºéƒ¨æ„ŸæŸ“æŒ‡æ ‡çš„å ³ç³».

Objective: To investigate the performance of using lung dynamic compliance (Cdyn) and airway resistance (RAW) levels to predict lung infection in elderly esophageal cancer patients who have undergone radiotherapy. Methods: A total of 298 elderly esophageal cancer patients who received radiotherapy at Shanxi Fenyang Hospital between October 2017 and July 2022 were retrospectively enrolled and their clinical data were collected. The patients were divided into an infection group (124 cases) and a non-infection group (174 cases) according to their status of lung infection. Then, in the infection group, CURB-65 score was used to assess the severity of the patients' lung infection and the patients were further divided into subgroups accordingly, with 36 cases in the mild infection subgroup, 58 cases in the moderate infection subgroup, and 30 cases in the severe infection subgroup. The levels of Cdyn, RAW, and infection indicators, including serum procalcitonin (PCT), interleukin-6 (IL-6), and angiotensin Ⅱ (Ang Ⅱ), were measured in both groups of patients and the differences in the findings were compared between the infection and the non-infection groups and among patients with infection of varying degrees of severity. The correlation between Cdyn and RAW and the levels of PCT, IL-6, and Ang Ⅱ was analyzed. Receiver operating characteristic (ROC) curve was used to evaluate the performance of predicting infection with Cdyn and RAW. Results: The Cdyn level of patients in the infection group was lower than that of patients in the non-infection group, while the RAW level of the infection group was higher than that of the non-infection group (P<0.05). Among the infection subgroup, the level of Cdyn of the mild infection subgroup was higher than those of the moderate and severe infection subgroups, while the levels of RAW, PCT, IL-6, and Ang Ⅱ of the mild infection subgroup were lower than those of the moderate severe subgroups. The level of Cdyn of the moderate infection subgroup was higher than that of the severe infection subgroup, while the RAW, PCT, IL-6, and Ang Ⅱ levels of the moderate infection subgroup were lower than those of the severe infection subgroup, with all difference being statistically significant (P<0.05). The Cdyn level of patients with lung infection was negatively correlated with PCT, IL-6, and Ang Ⅱ levels and the severity of infection (r=-0.501, -0.430, -0.367, and -0.484, respectively, P<0.05), while RAW was positively correlated with PCT, IL-6, and Ang Ⅱ levels and the severity of infection (r=0.483, 0.395, 0.374, and 0.423, respectively, P<0.05). The area under the curve (AUC) of Cdyn and RAW for predicting lung infection in elderly patients with esophageal cancer after radiotherapy were 0.898 (95% confidence interval [CI]: 0.857-0.930) and 0.823 (95% CI: 0.775-0.865), respectively, and the AUC of combined evaluation of Cdyn and RAW was 0.959 (95% CI: 0.930-0.979), which suggested that the predictive performance of combined evaluation was better than evaluation with Cdyn or RAW alone. Conclusion: When elderly esophageal cancer patients develop lung infection after radiotherapy, their Cdyn level is decreased, while the levels of RAW, PCT, IL-6, and Ang Ⅱ are increased. In addition, the levels of Cdyn and RAW are correlated with the PCT, IL-6, and Ang Ⅱ levels. The combined use of Cdyn and RAW shows good performance for predicting lung infection in patients.

[Analysis of WRKY transcription factor family based on full-length transcriptome sequencing in Polygonatum cyrtonema].

WRKY transcription factor family plays an important role in plant growth and development, secondary metabolite synthesis, and biotic and abiotic stress responses. The present study performed full-length transcriptome sequencing of Polygonatum cyrtonema by virtue of the PacBio SMRT high-throughput platform, identified the WRKY family by bioinformatics methods, and analyzed the physicochemical properties, subcellular localization, phylogeny, and conserved motifs. The results showed that 30.69 Gb nucleotide bases and 89 564 transcripts were obtained after redundancy removal. These transcripts had a mean length of 2 060 bp and an N50 value of 3 156 bp. Based on the full-length transcriptome sequencing data, 64 candidate proteins were selected from the WRKY transcription factor family, with the protein size of 92-1 027 aa, the relative molecular mass of 10 377.85-115 779.48 kDa, and the isoelectric point of 4.49-9.84. These WRKY family members were mostly located in the nucleus and belonged to the hydrophobic proteins. According to the phylogenetic analysis of WRKY family in P. cyrtonema and Arabidopsis thaliana, all WRKY family members were clustered into seven subfamilies and WRKY proteins from P. cyrtonema were distributed in different numbers in these seven subgroups. Expression pattern analysis confirmed that 40 WRKY family members had distinct expression patterns in the rhizomes of 1-and 3-year-old P. cyrtonema. Except for PcWRKY39, the expression of 39 WRKY family members was down-regulated in 3-year-old samples. In conclusion, this study provides abundant reference data for genetic research on P. cyrtonema and lays a foundation for the in-depth investigation of the biological functions of the WRKY family.

The impact of second-donor lymphocyte infusion on secondary graft failure after allogeneic hematopoietic stem cell transplantation through activation of Foxp3 and regulatory T cells.

Secondary graft failure (SGF) is a fatal complication of allogeneic hematopoietic stem cell transplantation without effective treatment methods, especially after haploidentical transplantation. This study aimed to analyze the efficacy of donor lymphocyte infusion (DLI) from a second donor in treating SGF and the underlying immune mechanisms. A second donor is a candidate donor who did not initially provide stem cells for HLA-matched sibling donor or HLA-haploidentical donor transplantation. We conducted a retrospective study of 237 patients with a median age of 38 years (range 9-56) for whom the degree of mixed chimerism (MC) and complete donor chimerism (CC), mRNA expression levels of Forkhead box P3 (Foxp3), and the proportion of regulatory T cells (Tregs) were regularly assessed. The median time to SGF was 62 days (range 41-117) after transplantation. Twenty-one patients with SGF received DLI, including 12 patients who initially received DLI from a second donor (i.e., a donor other than the transplantation [first] donor) and 9 patients who initially received DLI from the first donor but showed no response. Three of those 9 patients subsequently received DLI from a second donor. The incidence of acute GVHD and chronic GVHD induced by DLI from the second donor was significantly higher than that of DLI from the first donor (P = 0.006). Twenty-one patients with SGF exhibited synchronous MC, and the overall MC rate after transplantation was 65% (range 42%-85%).The proportion of Tregs significantly decreased in SGF patients, from a median of 2.61% ± 0.88% to 0.92% ± 0.23% at the indicated time point after transplantation (P = 0.03). Second-donor DLI resulted in a complete response (CR) in 13 patients, and MC gradually converted into CC; simultaneously, there was a significant increase in the mRNA level of Foxp3 and the proportion of Tregs (baseline, 0.92% ± 0.23% versus CR, 3.61% ± 0.82%; P = 0.01). For the patients who did not respond to DLI from either donor type, there was no significant change in donor chimerism, Foxp3 expression level or Treg proportion. Overall survival and disease-free survival 2 years after DLI were 66.7% ± 3.08% and 59.8% ± 4.11%, respectively. DLI from a second donor may be an effective treatment for SGF, and the mechanism is related to MC-to-CC conversion and activation of Foxp3 and Tregs.

Identification and functional analysis of novel oncogene DDX60L in pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer. Approximately 80% of patients initially diagnosed with locally advanced or metastatic disease survive only 4-11 months after diagnosis. Tremendous efforts have been made toward understanding the biology of PDAC. RESULTS: In this study, we first utilized next-generation sequencing technique and existing microarray datasets to identify significant differentially expressed genes between PDAC and non-tumor adjacent tissue. By comparing top significant survival genes in PDAC Gene Expression Profiling Interactive Analysis database and PDAC transcriptome data from patients, our integrated analysis discovered five potential central genes (i.e., MYEOV, KCNN4, FAM83A, S100A16, and DDX60L). Subsequently, we analyzed the cellular functions of the potential novel oncogenes MYEOV and DDX60L, which are highly expressed in PDAC cells. Notably, the knockdown of MYEOV and DDX60L significantly inhibited the metastasis of cancer cells and induced apoptosis. Further RNA sequencing analyses showed that massive signaling pathways, particularly the TNF signaling pathway and nuclear factor-kappa B (NF-κB) signaling pathway, were affected in siRNA-treated cancer cells. The siDDX60L and siMYEOV significantly inhibited the expression of chemokine CXCL2, which may potentially affect the tumor microenvironment in PDAC tissues. CONCLUSIONS: The present findings identified the novel oncogene DDX60L, which was highly expressed in PDAC. Transcriptome profiling through siRNA knockdown of DDX60L uncovered its functional roles in the PDAC in humans.

Confirmed Cryoglobulinemia and Hyperviscosity Syndrome Secondary to Multiple Myeloma-IgA Kappa from Routine Blood Test: a Case Report.

BACKGROUND: Cryoglobulins and hyperviscosity syndrome (HS) sometimes occur in multiple myeloma (MM), which are considered clinical emergencies. In laboratory practice, aspiration failure in routine blood tests sometimes occurs when the sample is inadequate. Here, a case of cryoglobulinemia and HS associated with advanced multiple myeloma was reported, which unusually is initially confirmed by aspiration failure in a routine blood test with sufficient sample. METHODS: A case of a 48-year-old female whose diagnosis of cryoglobulinemia and hyperviscosity syndrome secondary to MM-IgA kappa was confirmed from routine blood test. RESULTS: The sufficient sample for routine blood test could not be analyzed in a hematology analyzer due to aspiration failure, which was found to be caused by high viscosity and poor liquidity. A peripheral blood smear showed numerous non-cellular clouds, erythrocyte rouleaux formation, and plasma cell infiltration. After a water bath, the non-cellular clouds evidently disappeared, and the routine blood test was successfully conducted. Centrifugation of the sample for biochemical test, which had previously failed, was also possible. The case was confirmed as complications of cryoglobulinemia and HS associated with advanced MM, and the non-cellular clouds were identified as cryoglobulins. CONCLUSIONS: This case report provides an effective way for clinicians to deal with this kind of abnormal sample and limited but important laboratory evidence to establish early diagnosis of cryoglobulinemia and HS secondary to MM.

[Transcriptome and quality evaluation of Sichuan Dao-di herbs Zanthoxylum bungeanum].

"Huajiao" is dried ripe fruit peel of Zanthoxylum bungeanum or Z. schinifolium, is konwn as geoherbs, especially the "Dahongpao" cultivated in Hanyuan, Maoxian and Jiulong of Sichuan province. However, the genetic basis of Dao-di "Huajiao" is virtually unknown. The transcriptome of the fruit and leaf from Sichuan(Hanyuan, Jiulong, Lixian, Maoxian), Gansu(Wudu) province and Shaanxi(Fengxian) province was sequenced. Trinity de novo assembling resulted in a total of 177 616 unigenes. Through the KEGG, NR, SwissProt, Trembl, KOG/COG, GO, Pfam database comparision 106 644 annotated Unigene finally, 4 574 deferentially expressed genes were found in fruit between Sichuan and other provinces, including 3 740 up-regulated genes and 834 down-regulated genes. Among the up-regulated genes, 27 up-regulated genes were raleted to terpenoids, and 8 up-regulated genes were related to isoquinoline alkaloid bio-synthesis. Furthermore, it was also showed remarkable differences in groups which enrichment ratio of the diffe-rent expressed gene compared. The different expressed genes were annotated by the KEGG database into plant-pathogen interaction, plant hormone signal transduction and phenylpropanoid biosynthesis in fruit and leaf, but isoflavonoid bio-synthesis and betaine bio-synthesis were significantly different in fruit and leaf. The study laid a certain reference basis for comparison of quality and different expressed gene of Z. bungeanum from different groups.

Growth factor release by vesicular phospholipid gels: in-vitro results and application for rotator cuff repair in a rat model.

BACKGROUND: Biological augmentation of rotator cuff repair is of growing interest to improve biomechanical properties and prevent re-tearing. But intraoperative single shot growth factor application appears not sufficient to provide healing support in the physiologic growth factor expression peaks. The purpose of this study was to establish a sustained release of granulocyte-colony stimulating factor (G-CSF) from injectable vesicular phospholipid gels (VPGs) in vitro and to examine biocompatibility and influence on histology and biomechanical behavior of G-CSF loaded VPGs in a chronic supraspinatus tear rat model. METHODS: G-CSF loaded VPGs were produced by dual asymmetric centrifugation. In vitro the integrity, stability and release rate were analyzed. In vivo supraspinatus tendons of 60 rats were detached and after 3 weeks a transosseous refixation with G-CSF loaded VPGs augmentation (n = 15; control, placebo, 1 and 10 µg G-CSF/d) was performed. 6 weeks postoperatively the healing site was analyzed histologically (n = 9; H&E by modified MOVIN score/Collagen I/III) and biomechanically (n = 6). RESULTS: In vitro testing revealed stable proteins after centrifugation and a continuous G-CSF release of up to 4 weeks. Placebo VPGs showed histologically no negative side effects on the healing process. Histologically in vivo testing demonstrated significant advantages for G-CSF 1 µg/d but not for G-CSF 10 µg/d in Collagen III content (p = 0.035) and a higher Collagen I/III ratio compared to the other groups. Biomechanically G-CSF 1 µg/d revealed a significant higher load to failure ratio (p = 0.020) compared to control but no significant differences in stiffness. CONCLUSIONS: By use of VPGs a continuous growth factor release could be obtained in vitro. The in vivo results demonstrate an improvement of immunohistology and biomechanical properties with a low dose G-CSF application via VPG. The VPG itself was well tolerated and had no negative influence on the healing behavior. Due to the favorable properties (highly adhesive, injectable, biocompatible) VPGs are a very interesting option for biologic augmentation. The study may serve as basis for further research in growth factor application models.

[Isoliquiritigenin relaxes the cerebral basilar artery by enhancing BKCa current in spontaneously hypertensive rat: role of sGC/cGMP].

The purpose of the present study is to investigate the effect of isoliquiritigenin (ISL) on the cerebral basilar artery in spontaneously hypertensive rats (SHR). The change of SHR systolic pressure was measured by tail artery pressure measurement instrument before and after ISL intervention. After perfusion with 1 × 10(-5) mol/L phenylephrine (PE), 1 × 10(-5) mol/L PE + 1 × 10(-4) mol/L ISL and 1 × 10(-5) mol/L PE, the diameter of the cerebral basilar artery separated from SHR was measured by pressure myograph. The current of large-conductance calcium-activated potassium (BKCa) channel of SHR single vascular smooth muscle cell (VSMC) was recorded by whole-cell patch-clamp technique and the cGMP levels of basilar artery was evaluated by ELISA. The results showed that 1) after intervention with ISL for 14 days, the systolic pressure of SHR was decreased from (218.3 ± 1.6) mmHg to (119.2 ± 1.9) mmHg (P < 0.01), but there was no difference in systolic pressure between ISL-treated SHR and Wistar-Kyoto (WKY) rat; 2) 1 × 10(-4) mol/L ISL relaxed the SHR cerebral basilar artery (P < 0.01); 3) ISL significantly increased the outward current density of VSMC from SHR cerebral basilar artery (P < 0.01, n = 6), and the effect could be reversed by 1 × 10(-3) mol/L TEA (a BKCa channel inhibitor), but 3 × 10(-4) mol/L 4-AP (a Kv channel inhibitor) had no effect on the enhanced current density induced by ISL in VSMC; 4) 1 × 10(-5) mol/L Methylene blue (a sGC inhibitor) significantly inhibited the ISL-enhanced current density in VSMC (P < 0.05, n = 6); 5) ISL significantly increased the cGMP level of SHR basilar artery (P < 0.05, n = 6). The results suggest that the role of the ISL in relaxing the SHR cerebral basilar artery may be related to its effect in enhancing BKCa current by increasing the levels of cGMP in the VSMC.

Neurorehabilitation strategies: Assessing the impact on postoperative psychological state, pain, and complications in trigeminal neuralgia.

BACKGROUND: Trigeminal neuralgia is a difficult clinical situation marked by excruciating pain that requires efficient postoperative measures. In patients with trigeminal neuralgia, this study sought to investigate the effects of ongoing rehabilitation intervention on postoperative outcomes, including psychological state, pain, and complications. The aim was to provide new perspectives and treatment strategies for the management of this crippling illness. NEW METHOD: Between January 2021 and December 2022, 120 patients receiving treatment for trigeminal neuralgia were randomized to either the observation or control groups. The observation group received a continuous and comprehensive rehabilitation intervention that included elements of the control group's regimen, while the control group received standard health education and dietary guidance interventions through the use of a digital table method. The assessment of pain scales (VAS), self-rating depression scales (SDS), self-rating anxiety scales (SAS), and complication rates were all part of the postoperative follow-up. RESULTS: At seven days following surgery, there were no appreciable variations in the observation and control groups' VAS, SAS, and SDS scores (P > 0.05). Nevertheless, the observation group showed significantly lower VAS and SAS scores than the control group at 6 months and 1 year following surgery (P < 0.05). The observation group's SDS score was significantly lower than the control group's one year after surgery (P < 0.001). In comparison to the control group, the observation group also showed a lower overall complication rate (P < 0.05), especially in the cases of facial herpes and vertigo. COMPARISON WITH EXISTING METHODS: Our ongoing, all-encompassing rehabilitation approach demonstrated better results than current approaches in terms of long-lasting pain alleviation, enhanced mental health, and lower rates of complications in patients with trigeminal neuralgia following surgery. This implies that, in comparison to traditional methods, incorporating rehabilitation strategies may provide greater therapeutic benefits. CONCLUSION: Continuous comprehensive rehabilitation intervention can effectively reduce the degree of postoperative pain in patients with trigeminal neuralgia, help to regulate their psychological state, and reduce the occurrence of complications, which has certain clinical application value.

Infections associated with CAR-T cell therapy in patients with relapsed refractory multiple myeloma: Risks and prevention strategies.

BACKGROUND: Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a potent treatment for relapsed or refractory multiple myeloma, demonstrating significant clinical efficacy. Despite these advances, treatment-related toxicities, particularly infections, pose a significant challenge to patient safety. METHODS: This review synthesizes current knowledge on the mechanisms underlying post-CAR-T therapy infections, focusing on the interplay between immune dysfunction, host factors, and treatment-induced toxicity. It provides a comprehensive analysis of the temporal and individual variability in infection characteristics and the confounding clinical presentation of cytokine release syndrome. RESULTS: The review identifies that patients receiving CAR-T cells are at increased risk of concurrent infections due to the heterogeneity in infection characteristics across different time periods, individuals, and patient groups. It highlights the diagnostic and therapeutic complexities introduced by the overlapping symptoms of infection and cytokine release syndrome. CONCLUSION: To enhance the infection control post-CAR-T therapy, this review proposes preventive strategies tailored to the early and long-term management of patients. It underscores the need for a nuanced understanding of infection mechanisms and the importance of personalized prevention plans to improve clinical outcomes in multiple myeloma treatment.

Predicting occult lymph node metastasis in solid-predominantly invasive lung adenocarcinoma across multiple centers using radiomics-deep learning fusion model.

BACKGROUND: In solid-predominantly invasive lung adenocarcinoma (SPILAC), occult lymph node metastasis (OLNM) is pivotal for determining treatment strategies. This study seeks to develop and validate a fusion model combining radiomics and deep learning to predict OLNM preoperatively in SPILAC patients across multiple centers. METHODS: In this study, 1325 cT1a-bN0M0 SPILAC patients from six hospitals were retrospectively analyzed and divided into pathological nodal positive (pN+) and negative (pN-) groups. Three predictive models for OLNM were developed: a radiomics model employing decision trees and support vector machines; a deep learning model using ResNet-18, ResNet-34, ResNet-50, DenseNet-121, and Swin Transformer, initialized randomly or pre-trained on large-scale medical data; and a fusion model integrating both approaches using addition and concatenation techniques. The model performance was evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). RESULTS: All patients were assigned to four groups: training set (n = 470), internal validation set (n = 202), and independent test set 1 (n = 227) and 2 (n = 426). Among the 1325 patients, 478 (36%) had OLNM (pN+). The fusion model, combining radiomics with pre-trained ResNet-18 features via concatenation, outperformed others with an average AUC (aAUC) of 0.754 across validation and test sets, compared to aAUCs of 0.715 for the radiomics model and 0.676 for the deep learning model. CONCLUSION: The radiomics-deep learning fusion model showed promising ability to generalize in predicting OLNM from CT scans, potentially aiding personalized treatment for SPILAC patients across multiple centers.